Human-like Mice Livers Enhance Drug Development

(Ivanhoe Broadcast)—A new bioengineering technique that substitutes human liver cells in place of mice liver cells may allow researchers to develop more effective drugs prior to clinical trials. Stanford scientists evaluated mice with “humanized’ livers in the search for a potent hepatitis C drug cocktail. Over 150 million people are infected with HVC, the virus that causes hepatitis C and is the leading cause of liver transplant and liver cancer.

Researchers wanted to target HVC while overcoming obstacles of past mice drug testing. Unfortunately, the previous standard does not allow scientists to account for the interaction of multiple drugs and the metabolic functional differences between mouse and human livers.

"This gives us a new tool for improving the testing of drugs before they are given to people in clinical trials," the study's senior author, Gary Peltz, MD, PhD, professor of anesthesiology, pain and perioperative medicine said in a previously prepared statement. “All too often, drugs showing tremendous promise in preclinical animal assessments fail in human trials because of unforeseen safety problems. It's often not the drug itself, but one of its metabolites, that is responsible for a drug-induced toxicity."

The HVC trial drug, clemizole was tested using the modified mouse livers in an effort to develop a cheap, effective alternative to severe, costly treatments currently on the market.  Though prescribed as an antihistamine in the 1950s and 1960s, clemizole is being repurposed to target the HVC virus while interacting safely with other prescriptions—30 percent of the population 57 years and older take five prescriptions or more.

The mice livers were altered by researchers by killing liver cells and replacing them with human liver cells. The chimeric mice used in testing had varying levels of human cell integration. The study authors were able to distinguish how the human cells were interacting with drugs versus the mice cells and concluded that the bioengineered mice were accurate indicators of human performance and that clemizole is a viable drug for HVC trials.

The enhanced mice showed researchers effects that were previously masked due to the inherent differences in organ structure or created false alarms when transferred from mice to human candidates. The novel testing holds promise for future drug development targeting a plethora of additional ailments.

Source: Journal of Pharmacology and Experimental Therapeutics.
 

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